Muscular weakness is one of the major impairments limiting motor function following a hemispheric stroke. One mechanism that can contribute to muscle weakness is the structural changes of the motor unit, including reduction of fiber diameter, muscle fiber loss, and even motor axon loss and motoneuron reinnervation of paretic muscles. Currently, our knowledge of the extent of such motor unit structural change post-stroke is limited by the constraints associated with intramuscular recording techniques, which are both invasive and inefficient. A novel surface electromyogram (sEMG) recording and decomposition technique for motor unit analysis has recently been developed and tested in neurologically intact individuals. The system utilizes a unique surface electrode that is non-invasive and efficient, potentially yielding a large number of motor units simultaneously. Accordingly, the aims of this proposal are 1) To quantify the degree and frequency of the reduction in motor unit size in paretic muscle post-stroke. 2) To establish robust markers of motoneuron reinnervation in paretic muscle of stroke survivors. We will record the sEMG signals of both paretic and contralateral first dorsal interosseous muscles of 32 stroke survivors during isometric contractions at specified force levels, and we will also record the sEMG of 32 neurologically intact age-matched control subjects. We will extract single motor unit discharge activities using the novel sEMG decomposition algorithm, and estimate motor unit shape characteristics using the spike triggered averaging techniques. To address Aim 1, we will calculate key motor unit action potential (MUAP) parameters, including peak-peak amplitude, duration, and root mean squared values, as estimates the motor unit size. To address Aim 2, we will quantify the polyphasic properties (i.e., the number of peaks) of the MUAP as an estimate of motoneuron reinnervation. We will also examine the association between the structural changes in motor units and the severity of motor impairment. We hypothesize that the motor unit size in the paretic muscle is reduced, because of fiber size reduction and muscle fiber loss, and that the polyphasic changes (i.e., a larger number of peaks) in the MUAP are also more visible in the paretic muscle following a stroke. The proposed research will provide important information regarding the role of peripheral motor unit structural changes in muscle weakness. The novel and non-invasive techniques used here will provide an efficient way to systematically examine changes in motor unit characteristics, and can potentially serve as a diagnostic tool to distinguish central vs. peripheral origins of muscle weakness in stroke. The proposed work can thus provide a rationale for differentially targeted rehabilitation therapies with a potential to maximize functional recovery of stroke survivors. i